Clinical Reasoning: A 28-Year-Old Man With Seizures and Thalamic Lesions

This case involves a 28-year-old Black man who presented with new-onset seizures and bilateral medial temporal lobe hyperintensities on brain MRI, initially raising concern for viral encephalitis. CSF analysis revealed mild lymphocytic pleocytosis, but extensive infectious testing was negative. One year later, he developed acute right-sided weakness, and an MRI showed an enhancing FLAIR/T2 hyperintense mass-like lesion in the left thalamus. Stereotactic biopsy demonstrated reactive changes and Periodic acid-Schiff diastase (PASD)-positive macrophages, prompting consideration of atypical infectious or inflammatory etiologies. Despite empiric antibiotic treatment, his symptoms recurred 8 months later with new T2/FLAIR hyperintense lesions in the bilateral thalami and internal capsule, accompanied by mucocutaneous findings. He responded well to immunosuppressive therapy, with significant clinical and radiographic improvement. This case highlights the challenges of diagnosing relapsing neurologic syndromes with overlapping infectious, inflammatory, and neoplastic features and underscores the importance of integrating imaging, histopathology, and clinical evolution to reach a definitive diagnosis.